We propose to continue a feasibility study of the determination of the structures of biomacromolecules in noncrystalline environments. We will use two dimensional NMR experiments, in conjunction with distance geometry calculations and computer graphics, to measure the solution structure of peptides, nucleotides and small proteins. High resolution proton NMR spectra contain enough information to determine molecular geometries with an accuracy of a few angstroms. The important steps to obtain this information are: assignment of the proton NMR signals, measurement of NOEs for short distance determinations, use of paramagnetic reagents for long distance measurements, calculation of molecular coordinates from the distances using distance geometry, and refinement of the molecular structure using energy calculations, molecular dynamics, and interactive computer graphics. Experiments are described to improve the spectral assignment procedures and to assess the feasibility of measuring a wide range of distances. The complications introduced by molecular motion are discussed. The effort will be pointed toward structural and dynamic comparisons of engineered proteins and unusual nucleic acid structures. We hope these experiments will identify the quantitative limits of, and prospects for, the emerging NMR technology. It should have a significant impact on questions of molecular design. The project is a large one, requiring access to a high field spectrometer and considerable computational power. Because of the enormous potential of the method and the very significant effort required to bring it to maturity, we propose to continue the project as a Resource-Related Research Project.